METHODS: Precision signal generation and targeted cellular manipulation was used in conjunction with high spatiotemporal mesoscale Ca2+ imaging in the endothelium of intact blood vessels.
RESULTS: Multiple mechanisms maintain communication so that Ca2+ wave propagation occurs irrespective of the status of connectivity among cells. Between adjoining cells, regenerative IP3-induced IP3 production transmits Ca2+ signals and explains the propagated vasodilation that underlies the increased blood flow accompanying tissue activity. The inositide is itself sufficient to evoke regenerative phospholipase C-dependent Ca2+ waves across coupled cells. None of gap junctions, Ca2+ diffusion or the release of extracellular messengers is required to support this type of intercellular Ca2+ signalling. In contrast, when discontinuities exist between cells, ATP released as a diffusible extracellular messenger transmits Ca2+ signals across the discontinuity and drives propagated vasodilation.
CONCLUSIONS: These results show that signalling switches underlie endothelial cell-to-cell signal transmission and reveal how communication is maintained in the face of endothelial damage. The findings provide a new framework for understanding wave propagation and cell signalling in the endothelium.
方法:精确信号产生和靶向细胞操作与完整血管内皮中的高时空中尺度Ca2成像结合使用。
结果:多种机制维持通信,使得Ca2+波传播发生,而与小区之间的连接状态无关。在相邻的细胞之间,再生IP3诱导的IP3产生传递Ca2信号,并解释了伴随组织活动的血流增加的基础上的血管舒张。肌醇肽本身足以在偶联的细胞中引起再生的磷脂酶C依赖性Ca2波。没有任何间隙连接,需要Ca2+扩散或细胞外信使的释放来支持这种类型的细胞间Ca2+信号传导。相比之下,当细胞之间存在不连续性时,作为可扩散的细胞外信使释放的ATP通过不连续传递Ca2信号并驱动传播的血管舒张。
结论:这些结果表明,信号转换是内皮细胞到细胞信号传递的基础,并揭示了在内皮损伤面前如何维持通信。这些发现为理解内皮中的波传播和细胞信号提供了新的框架。